Dimethylformamide → 4-[4-(3-Indolyl)piperidinomethyl]-2-mesylaminothiazole

HRID 1252072Notes

Reaction equation

HRID 1252072 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[NH:16][CH:15]=3)[CH2:10][CH2:9]2)[N:6]=1.C(N(CC)CC)C.CN(C)C=O.[S:35](Cl)([CH3:38])(=[O:37])=[O:36]>C(Cl)Cl.O>[NH:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14]([CH:11]2[CH2:12][CH2:13][N:8]([CH2:7][C:5]3[N:6]=[C:2]([NH:1][S:35]([CH3:38])(=[O:37])=[O:36])[S:3][CH:4]=3)[CH2:9][CH2:10]2)=[CH:15]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 31297Methanesulfonyl chloride2×HCID 141297964-((4-(1H-Indol-3-yl)piperidin-1-yl)methyl)thiazol-2-amine

Product 1

HCID 98005844-[4-(3-Indolyl)piperidinomethyl]-2-mesylaminothiazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 2-amino-4-[4-(3-indolyl)piperidinomethyl]thiazole (1.73 g), triethylamine (3.1 ml) and N,N-dimethylformamide (15 ml) was added dropwise a solution of mesyl chloride (0.86 ml) in methylene chloride (1 ml) at 5° to 7° C. with stirring. The mixture was further stirred at that temperature for 2 hours, after which a solution of mesyl chloride (0.34 ml) in methylene chloride (0.5 ml) was added. The reaction mixture was further stirred at the same temperature for 1.5 hours. Following addition of water (50 ml), the reaction mixture was extracted with a mixture of chloroform and methanol (60 ml, 10:1 V/V) twice. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (40 ml) and, then, 10% aqueous sodium hydroxide solution (20 ml) was added gradually thereto. The mixture was stirred at ambient temperature overnight. The reaction mixture was then adjusted to pH 7.0 with diluted hydrochloric acid and extracted with a mixture of chloroform and methanol (100 ml, 10:1 V/V). The organic layer was separated, washed with water, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was subjected to column chromatography on silica gel, followed by elution with a mixture of chloroform and methanol (10:1 V/V). The eluate gave 4-[4-(3-indolyl)piperidinomethyl]-2-mesylaminothiazole (480 mg).

Workup

  1. stirringThe mixture was further stirred at that temperature for 2 hours
  2. stirringThe reaction mixture was further stirred at the same temperature for 1.5 hours
  3. extractionthe reaction mixture was extracted with a mixture of chloroform and methanol (60 ml, 10:1 V/V) twice
  4. washThe extract was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in tetrahydrofuran (40 ml)
  8. addition10% aqueous sodium hydroxide solution (20 ml) was added gradually
  9. stirringThe mixture was stirred at ambient temperature overnight
  10. extractionextracted with a mixture of chloroform and methanol (100 ml, 10:1 V/V)
  11. customThe organic layer was separated
  12. washwashed with water
  13. dry with materialdried over magnesium sulfate
  14. distillationThe solvent was distilled off under reduced pressure
  15. washfollowed by elution with a mixture of chloroform and methanol (10:1 V/V)

Sources & evidence

ORD record
ord-75a0dc787c494a05a58a7266cd1c18a2
Source dataset
uspto-grants-1988_05
Patent number
US04742057

Reaction notes

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